The arylpiperazinyl butyrophenone derivative with which the present inventive method is concerned has been referred to in the prior art as BMY 14802 and also MJ 14802. The synthesis of the compound and a disclosure of its antipsychotic properties are described by Yevich, et al., in U.S. Pat. No. 4,605,655. ##STR1##
Boissard, et al., have disclosed the use of BMY 14802 for treating various disorders resulting from brain ischemia in U.S. Pat. No. 5,055,470.
McMillen, et al., have studied various antipsychotic drugs, including BMY 14802, in animal models of aggression and suggest that a relationship exists between antiaggressive activity and a potential for anxiolytic effects; e.g. see Drug Rev. Res., 12(1), 53-62 (1988). McMillen, et al., also disclosed in J. Pharm. Pharmacol., 40: 885-887 (1988); that BMY 14802 demonstrated activity in reversing neuroleptic-induced catalepsy in a study involving members of the azapirone class of novel arylpiperazines such as the clinical anxiolytic agents buspirone, gepirone and ipsapirone. McMillen suggested that the anti-catalepsy activity correlates with the arylpiperazine's having anti-aggression action.
The archetypical arylpiperazine anxiolytic drug is buspirone. Clinical studies with buspirone however, indicate that its anxiolytic efficacy is diminished in patients being withdrawn from benzodiazepine treatment. [Schweizer, et al., Am. J. Psychiatry, 143: 12, 1590-1592 (1986).] Buspirone, and BMY 14802 alike, have no clinically significant benzodiazepine receptor activity. Similar conclusions were reached for a related azapirone arylpiperazine anxiolytic, ipsapirone on the basis of animal studies [Goudie, et al., Psychopharmacology, 103: 529-537 (1991).] Against this background, antianxiety effects of BMY 14802 would not be expected in benzodiazepine-withdrawn patients.
Due to wide usage of the benzodiazepine class of anxiolytics, in spite of their acknowledged liabilities, there exists a need for agents that are effective in treating the anxiety experienced by patients during benzodiazepine withdrawal. Costall, et al., [Pharmacol. Biochem. Behav., 34: 769-778 (1989)] reported that the non-arylpiperazine anxiolytic agent ondansetron ##STR2## demonstrated anxiolytic action in an animal model of anxiety following benzodiazepine withdrawal.
No suggestion exists in this background art that would make obvious in any way the existence of a therapeutic advantage of the arylpiperazinyl antipsychotic agent BMY 14802 over recognized arylpiperazine anxiolytics for treatment of a population being withdrawn from benzodiazepine exposure.